dc.contributor.author |
Ribas i Fortuny, Judit |
dc.contributor.author |
Ni, Xiaohua |
dc.contributor.author |
Castanares, Mark |
dc.contributor.author |
Liu, Minzhi M. |
dc.contributor.author |
Esopi, David |
dc.contributor.author |
Yegnasubramanian, Srinivasan |
dc.contributor.author |
Rodriguez, Ronald |
dc.contributor.author |
Mendell, Joshua T. |
dc.contributor.author |
Lupold, Shawn E. |
dc.date |
2012-12-11T11:22:06Z |
dc.date |
2012-12-11T11:22:06Z |
dc.date |
2012 |
dc.identifier |
0305-1048 |
dc.identifier |
http://hdl.handle.net/10459.1/46370 |
dc.identifier |
https://doi.org/10.1093/nar/gks308 |
dc.identifier.uri |
http://hdl.handle.net/10459.1/46370 |
dc.description |
miR-21 is the most commonly over-expressed microRNA (miRNA) in cancer and a proven oncogene. Hsa-miR-21 is located on chromosome 17q23.2, immediately downstream of the vacuole membrane protein-1 (VMP1) gene, also known as TMEM49. VMP1 transcripts initiate ∼130 kb upstream of miR-21, are spliced, and polyadenylated only a few hundred base pairs upstream of the miR-21 hairpin. On the other hand, primary miR-21 transcripts (pri-miR-21) originate within the last introns of VMP1, but bypass VMP1 polyadenylation signals to include the miR-21 hairpin. Here, we report that VMP1 transcripts can also bypass these polyadenylation signals to include miR-21, thus providing a novel and independently regulated source of miR-21, termed VMP1–miR-21. Northern blotting, gene-specific RT-PCR, RNA pull-down and DNA branching assays support that VMP1–miR-21 is expressed at significant levels in a number of cancer cell lines and that it is processed by the Microprocessor complex to produce mature miR-21. VMP1 and pri-miR-21 are induced by common stimuli, such as phorbol-12-myristate-13-acetate (PMA) and androgens, but show differential responses to some stimuli such as epigenetic modifying agents. Collectively, these results indicate that miR-21 is a unique miRNA capable of being regulated by alternative polyadenylation and two independent gene promoters. |
dc.description |
The ‘National Institutes of Health/National Cancer Institute’ [5R01CA143299 to S.E.L., 5P50CA058236 to S.E.L. (Project 1)]; Department of Defense Prostate Cancer Research Fund [W81XWH-08-13-5 to S.E.L.]; Patrick C. Walsh Prostate Cancer Research Fund (to S.E.L.); Spanish ‘Ministerio de Ciencia e Innovación’ [SAF2011-29730 to J.R.]. Funding for open access charge: National Institutes of Health/NCI R01CA143299. |
dc.language |
eng |
dc.publisher |
Oxford University Press |
dc.relation |
MICINN/PN2008-2011/SAF2011-29730 |
dc.relation |
Reproducció del document publicat a: https://doi.org/10.1093/nar/gks308 |
dc.relation |
Nucleic Acids Research, 2012, vol. 40, núm. 14, p. 6821-6833 |
dc.rights |
cc-by-nc, (c) Ribas et al., 2012 |
dc.rights |
http://creativecommons.org/licenses/by-nc/3.0/es/deed.ca |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.subject |
miR-21 |
dc.subject |
RNA |
dc.subject |
Càncer |
dc.subject |
Gens |
dc.subject |
ADN |
dc.subject |
Cicle cel·lular |
dc.title |
A novel source for miR-21 expression through the alternative polyadenylation of VMP1 gene transcripts |
dc.type |
article |
dc.type |
publishedVersion |